DHEA in bone: the role in osteoporosis and fracture healing

Dehydroepiandrosterone (DHEA) is a metabolic intermediate in the biosynthesis of estrogens and androgens with a past clouded in controversy and bold claims. It was once touted as a wonder drug, a fountain of youth that could cure all ailments. However, in the 1980s DHEA was banned by the FDA given a lack of documented health benefits and long-term use data. DHEA had a revival in 1994 when it was released for open market sale as a nutritional supplement under the Dietary Supplement Health and Safety Act. Since that time, there has been encouraging research on the hormone, including randomized controlled trials and subsequent meta-analyses on various conditions that DHEA may benefit. Bone health has been of particular interest, as many of the metabolites of DHEA are known to be involved in bone homeostasis, specifically estrogen and testosterone. Studies demonstrate a significant association between DHEA and increased bone mineral density, likely due to DHEA's ability to increase osteoblast activity and insulin like growth factor 1 (IGF-1) expression. Interestingly, IGF-1 is also known to improve fracture healing, though DHEA, a potent stimulator of IGF-1, has never been tested in this scenario. The aim of this review is to discuss the history and mechanisms of DHEA as they relate to the skeletal system, and to evaluate if DHEA has any role in treating fractures.